Generally, in the case of conducting analysis based on a chemical reaction, it is necessary that liquids such as samples and reactive reagents be quantitatively weighed and collected so as to be subjected to quantitative reaction so that precise analysis results can be obtained. In particular, as conducting microanalysis such as blood analysis, it is necessary that a liquid such as specimen or a reactive reagent be weighed with high precision so that it can be supplied to a reaction site.
Hitherto, substances in a liquid specimen have been quantified by the following operation: a liquid such as a specimen or a reactive reagent is weighed using a collecting device (pipet, micropipet, syringe, etc.); a given amount of the liquid weighed is supplied to a reaction vessel; reaction is performed; and thus a target substances in the specimen are quantified based on reaction signals.
In general, a conventional wet chemistry analysis method is complicated, and the handling and procedures relating to apparatuses used for analysis are not simple. For instance, in the case of blood analysis, it is necessary to use a combination of many reagent solutions handled in different ways so as to measure a single blood component. When measuring glycohemoglobin (HbAlc) in blood using a blood analyzer (7170; Hitachi), 240 μl of a reagent solution 1 and 8.0 μl of HbAlc are separately collected and weighed, mixed, and allowed to react with each other at 37° C. for 5 minutes. Then, 80 μl of a reagent solution 2 is weighed, and is added thereto. After being kept at 37° C. for 5 minutes, the resultant is quantified by a 2 point-end method (dominant wavelength: 450 nm; complementary wavelength: 800 nm) (International Publication WO02/018953).
To measure glycohemoglobin (HbAlc) in blood as described above, a collecting and weighing device (1), a vessel for mixing a specimen and a reagent, and operation for supplying a specimen liquid, for example, are required, making the configuration and the operation for the measurement complicated. In addition, many forms of disposal waste (chips, mixing vessels, washes, etc.) are generated due to the measurement, and this has been problematic.
On the other hand, dry chemistry analysis method has been developed, wherein reagents and the like, which are necessary for detection of a specific component, are contained in a dry state (“11. Other analysis methods (Sonota no Bunseki Ho): (1) Dry Chemistry,” Yuzo Iwata, “Manual for Clinical Chemistry Practice (Rinsho Kagaku Jissen Manual),” Igaku Shoin, 1993, “Modern Medical Laboratory (Kensa To Gijutsu), extra number,” vol. 21, no. 5, pp. 328-333). In accordance with the dry chemistry analysis method, all reagents necessary for qualitative/quantitative analysis are incorporated into an analysis element such as reagent paper, a disposable electrode, or a disposable magnetic material. Basically, a disposable analysis element capable of measuring a single component from a single specimen is used. Thus, rapid blood analysis using a relatively small amount of blood (about 10 μl) can readily be conducted (JP Patent Publication (Kokai) No. 8-122335 A (1996)). A large number of analyzers using a dry chemistry analysis method have been developed and commercialized. Examples thereof that are commercially available include Fuji Drychem (Fujifilm), Ektachem (Eastman Kodak, U.S.), Drylabo (Konica), Spotchem (Kyoto Daiichi Kagaku), Reflotron (Boehringer Mannheim, Germany), and Seralyzer (Miles Laboratories; U.S.). Upon dry chemistry analysis, operation whereby a specimen liquid is supplied so that it can be mixed with a reagent is not required. However, a collecting and weighing device and a collecting operation are still required.
Further, in recent years, home care has been proposed as a response to a sharp increase in medical costs due to the rapid transition to an aging society and the development of advanced medical therapies. In addition, home care, which is supposed to be a core of the future medical system, has been discussed in terms of specific ways of implementing it. To correspond to such situation, in the home care system, it is preferable to use a blood analysis method whereby a plurality of components can be rapidly measured with good precision using a minute amount of blood and a small-sized apparatus in a convenient manner.
Thus, to solve the above problems, application of a μTAS (micro total analysis system) technology, whereby a conventionally used analyzer can be downsized and a trace amount of a liquid reagent is allowed to react, has been discussed. With μTAS technology, in order to collect a minute amount of a specimen such as blood or the like, a groove is formed on the surface of a chip made of glass, silicon, or resin, the size of which is several to ten square centimeters. Then, a reagent solution or a specimen is poured into the groove such that separation or reaction is carried out. Thus, analysis of a minute amount of a sample is conducted (JP Patent Publication (Kokai) No. 2-245655 A (1990), JP Patent Publication (Kokai) No. 3-226666 A (1991), JP Patent Publication (Kokai) No. 8-233778 A (1996), JP Patent Publication (Kokai) No. 10-142177 A (1998), and Analytical Chem. 69, 2626-2630 (1997) Aclara Biosciences). When using this technique, a minute amount of a sample and a reagent that is necessary for detection must be collected and weighed in a chip. However, since the amount of a specimen liquid handled is extremely small, it is difficult to quantitatively collect and weigh such liquid. Thus, a complicated configuration is required to collect and weigh such liquid, resulting in a complicated operation for handling the configuration, which has been problematic.
In JP Patent Publication (Kokai) No. 2004-163104 A, a structure for collecting and weighing a small amount of a liquid is provided for a channel of a microchip so that capillarity (capillary repulsion) generated by the liquid in the channel is utilized. In accordance with JP Patent Publication (Kokai) No. 2004-163104 A, a structure for collecting and weighing a small amount of a liquid is provided for various types of apparatuses in which it is necessary to handle a liquid in a conventional quantitative manner such that reduction of the dead volume of a sample, downsizing of the apparatus used in its entirety, and costsaving can be achieved. However, in the case of the technique disclosed in JP Patent Publication (Kokai) No. 2004-163104 A, it is necessary to design a channel in a microchip, impart hydrophilicity or hydrophobicity to the channel, and feed a liquid into the channel by air pressure. Thus, it is difficult to say that such method is a convenient method for weighing a small amount of liquid quantitatively.
Further, as techniques for collecting and weighing a trace amount of liquid include those disclosed in JP Patent Publication (Kokai) No. 2002-357616 A and JP Patent Publication (Kokai) No. 2004-157097 A, for example. When these techniques are employed, a trace amount of liquid can be quantitatively handled with a microchip provided with a plurality of fluid channels in which liquid continuously flows. However, a liquid transport system is needed for liquid operation and various construction in microchip.